Clinicians have long been aware of the high rate of relapse in the first three months of treatment for opiate dependence and its theoretical relationship to a persistent, but loosely defined, dysregulated state consequent to opiate withdrawal. The term allostasis has been applied to the changes in the HPA axis and the brain reward system associated with opiate dependence that may persist following detoxification. The normal homeostasis of the HPA axis is disturbed, responses to natural rewards (e.g., food, sex, etc.) are dampened, the response to drug-related stimuli is markedly enhanced, and patients complain of negative mood (anhedonia). The duration of various elements of dysregulation after detoxification, in animal models and in patients, is uncertain; as is the question of how & whether findings in the rodent can be translated into clinically meaningful data. Importantly, it i unclear if these data have prognostic significance; and, in particular, whether they are relevant to patients dependent on prescription opioids. The proposed study will follow a population of recently detoxified male and female patients with prescription opioid dependence through a one month period of inpatient drug rehabilitation treatment, 3 additional months of extended residential care at the Caron Foundation (Wernersville, PA), and 1 and 3 months post-discharge. Recent experience indicates that 5 patients/month would be eligible for enrollment in the study. Those patients likely to transition from the 30-day program to extended care are typically identified by the 10th day of the 30 day program. 5% of these patients have historically failed to complete the extended care program. The proposed study follows upon the results of a pilot study that included: 1) assessments of frontal cortical and psychophysiological responses to slide sets of drug cues and natural rewards; 2) diurnal cortisol; and, 3) 8 days of objective an subjective measures of sleep, as well as self-reported mood, stress and craving in 7 recently detoxified patients dependent on prescription opioids (DPO), 7 DPO patients who had been in supervised drug-free residential care for 90+ days, and 7 normal control participants (Ps). The statistically significant differences between the groups on these measures support the need for a longitudinal study of these variables in patients over time. The overall objective of the study will be to compare the baseline CNS responses, diurnal cortisol, sleep & daily and within- day variability of mood, stress and craving of recently detoxified patients dependent upon prescription opioids, with normal control Ps; and, to monitor these measures in the patients over time, from ten days post detox through the maximum period of supervised drug-free residence. New statistical methods for the analysis of intensively-measured processes will be used to advance understanding of the temporal relationships between these measures, and their possible predictive relationship to drug-using status one and three months after discharge. The findings from the proposed research will help to advance evidence-based, treatment guidelines on prescription opioid dependence, as well as translational research on addictive disorders.